s0304 induct chemo then chemo-rt in pts w/locally advanced adenocarcinoma of the rectum

Conditions: Colorectal Cancer

Summary: rationale: drugs used in chemotherapy, such as irinotecan, leucovorin, fluorouracil, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. radiation therapy uses high-energy x-rays to damage tumor cells. combining radiation therapy with chemotherapy may kill more tumor cells. purpose: this phase ii trial is studying how well different regimens of induction chemotherapy followed by chemoradiotherapy work in treating patients with locally advanced adenocarcinoma of the rectum.

objectives: * determine the feasibility of obtaining a pre-treatment determination of intratumoral molecular markers (ts, dpd, and ercc-1) for use in selection of the appropriate regimen for induction cytotoxic combination chemotherapy in patients with ct3-4 rectal adenocarcinoma. * determine the response probability (unconfirmed, complete and partial) in patients treated with targeted induction cytotoxic chemotherapy. * determine the toxicity of targeted induction cytotoxic chemotherapy and chemoradiotherapy in these patients. * determine the response probability in these patients treated with chemoradiotherapy. outline: this is a multicenter study. * induction chemotherapy: patients are assigned to 1 of 3 treatment groups based on molecular analysis of the pretreatment tumor specimen. * group i (lower likelihood of resistance to a fluorouracil-based regimen): patients receive irinotecan iv over 90 minutes and leucovorin calcium iv over 2 hours on day 1 and fluorouracil iv over 46 hours beginning on day 1. * group ii (higher likelihood of resistance to a fluorouracil-based regimen): patients receive oxaliplatin iv over 2 hours and irinotecan iv over 90 minutes on day 1. * group iii (high likelihood of sensitivity to oxaliplatin and fluorouracil therapy): patients receive oxaliplatin iv over 90 minutes and leucovorin calcium iv over 2 hours on day 1 and fluorouracil iv over 46 hours beginning on day 1. treatment in all groups repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. patients are evaluated for response approximately 2 weeks after the completion of induction chemotherapy. patients with stable disease or better receive chemoradiotherapy. * chemoradiotherapy: beginning approximately 3 weeks after the completion of induction chemotherapy, patients receive oral capecitabine twice daily continuously for 5 weeks and concurrent radiotherapy once daily 5 days a week for 5 weeks. after chemoradiotherapy, patients may undergo attempted surgical resection at the discretion of the treating physician. patients are followed every 3 months for 1 year and then every 6 months for 2 years. projected accrual: a total of 10-65 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed primary adenocarcinoma of the rectum * locally advanced disease (clinical t3-4, n0-2, m0) based on at least 1 of the following criteria: * clinically fixed tumors on rectal examination with tumor adherent to the pelvic sidewall and/or sacrum * sciatica attributed to sacral root invasion with ct scan/mri evidence of the lack of clear tissue plane is considered evidence of fixation * hydronephrosis on ct scan or intravenous pyelogram of ureteric or bladder invasion by cystoscopy and cytology or biopsy * invasion into the prostate, vagina, or uterus * transmural penetration of tumor through the muscularis propria as evidenced by ct scan or mri and endorectal ultrasound * distal border of the tumor must be at or below the peritoneal reflection (within 12 cm of the anal verge) by proctoscopic examination * measurable disease by x-ray, scans, or physical examination * available tumor tissue to determine molecular profile of the tumor before study treatment * no clinical evidence of high-grade (lumen diameter \< 1 cm) large bowel obstruction unless a diverting colostomy has been performed patient characteristics: age * 18 and over performance status * zubrod 0-2 life expectancy * not specified hematopoietic * wbc ≥ 3,500/mm\^3 * absolute neutrophil count ≥ 1,500/mm\^3 * platelet count ≥100,000/mm\^3 hepatic * bilirubin ≤ 1.5 times upper limit of normal (uln) * sgot or sgpt ≤ 2.5 times uln * alkaline phosphatase ≤ 2.5 times uln renal * see disease characteristics * creatinine ≤ 1.5 times uln or * estimated creatinine clearance \> 50 ml/min cardiovascular * no significant cardiac disease * no recent myocardial infarction gastrointestinal * see disease characteristics * able to swallow oral medication * no active inflammatory bowel disease other * not pregnant or nursing * fertile patients must use effective contraception * no other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * no prior unanticipated severe reaction to study drugs * no known dihydropyrimidine dehydrogenase deficiency * no serious uncontrolled infection * no other serious medical illness that would preclude study treatment prior concurrent therapy: biologic therapy * not specified chemotherapy * no prior chemotherapy for colon or rectal cancer endocrine therapy * not specified radiotherapy * no prior pelvic radiotherapy * no prior intra-operative radiotherapy or brachytherapy * no concurrent intra-operative radiotherapy or brachytherapy * no concurrent intensity-modulated radiotherapy surgery * see disease characteristics * see radiotherapy

Keywords: stage ii rectal cancer stage iii rectal cancer adenocarcinoma of the rectum